Aerial part of Houttuynia cordata reverses memory impairment by regulating amyloid beta accumulation and neuroinflammation in Alzheimer's disease model

Alzheimer's disease (AD) is the most common neurodegenerative disease characterized by amyloid-β (Aβ) deposition, accompanied by neuroinflammation and memory dysfunction. Houttuyniae Herba (aerial parts of Houttuynia cordata, also known as fish mint; HH), an herbal medicine traditionally used to treat fever, urinary disorders, and pus, is revealed to protect neurons from Aβ toxicity and regulate cholinergic dysfunction in AD models. In this study, we aimed to investigate the effects of HH on excessive accumulation of Aβ followed by neuroinflammation, synaptic degeneration, and memory impairment. Two-month-old 5xFAD transgenic mice were administered HH at 100 mg/kg for 4 months. We observed that HH treatment ameliorated memory impairment and reduced Aβ deposits in the brains of the mice. HH directly inhibited Aβ aggregation in vitro using the Thioflavin T assay and indirectly suppressed the amyloidogenic pathway by increasing alpha-secretase expression in the mice brain. In addition, HH exerted antineuroinflammatory effects by reducing of glial activation and p38 phosphorylation. Moreover, HH treatment increased the expression of synaptophysin, a presynaptic marker protein. Overall, HH alleviates memory impairment in AD by facilitating nonamyloidogenic pathway and inhibiting neuroinflammation. Therefore, we suggest that HH can be a promising herbal drug for patients with AD requiring multifaceted improvement.